Galactose metabolism is essential to life for humans, higher animals, microorganisms and plants. Several inherited defects in the metabolism of galactose in humans are known, all of which involve impairments in the activities of enzymes required for galactose metabolism by the Leloir pathway . The mechanisms by which two enzymes catalyze steps in the metabolism are major subjects of research. Phosphoryl and alkylphosphoryl group transfer reactions art also essential enzymatic processes in the biosynthesis of most cellular constituents and in signal transduction. Uncontrolled cellular proliferation and impaired development often involve defects in the metabolism of phosphates. The nature of the transitions states for enzymatic phosphoryl and alkylphosphoryl group transfer reactions will be examined using substrate analogs and kinetic methods. The means by which these enzymes use binding energy to catalyze reactions will be examined by x-ray crystallography, infrared and nuclear magnetic resonance spectroscopy and site directed mutagenesis, as well as by kinetic and other traditional methods.